Adaptations to intra-thoracic fluid monitoring algorithm

ABSTRACT

Adaptations to an intra-thoracic fluid-status-trend indication and/or alert algorithm are disclosed. Some embodiments monitor fluid levels in heart failure patients and others suffering from pulmonary edema and the like. Some embodiments reset a cumulative fluid index when a short-term intra-thoracic impedance value exceeds a baseline impedance value minus a predetermined positive hysteresis value. Many device, system, and method embodiments hereof serve to reduce the number of false positive alerts while retaining the desired sensitivity.

BACKGROUND

Some embodiments disclosed herein relate generally to enhancing therapy.Impedance monitoring is often used with implantable medical devices andin external monitoring devices to determine physiologic conditions thatare of clinical significance or interest. For example, intra-thoracicimpedance measurements can give a good indication of the fluid status ofpatients, with decreases in impedance being indicative of increases influid content. Knowledge of a patient's long-term impedance measurementsand changes therein are a valuable clinical indicator of a patient'shealth. Herein “intra-thoracic” means within or across a portion of aheart, lungs and/or the pulmonary bed. For example, a subcutaneous orsub-muscular electrode, a transvenous electrode, a pericardial electrodeor the like is used to measure impedance values of a patient.

The accumulation of fluid may be an indication of a failing heartcirculation or other medical conditions. There are several physiologicmalfunctions or diseases that can cause or affect the accumulation offluid. In general, fluid accumulation is a failure or over-response ofthe homeostatic process within the body. The body normally prevents thebuild up of fluids by maintaining adequate pressures and concentrationsof salt and proteins and by actively removing excess fluid. Fluidaccumulation can occur, for example, when the body's mechanisms forpreventing fluid accumulation are affected by disease, such as heartfailure, left-sided myocardial infarction, high blood pressure, altitudesickness, emphysema (all of which affect pressures), cancers that affectthe lymphatic system, and diseases that disrupt the proteinconcentrations. As a result, providing an adequate monitor of thepatient's fluid status can provide physicians and patients with a betterdiagnostic tool to manage disease.

Upon detection of predetermined impedance values indicating abnormalfluid accumulation, the patient can be notified to seek professionalcare. In this way, a clinician is able to proactively address thepatient's fluid accumulation, which may be the result of cardiacdecompensation during heart failure. This allows patients to receiveprofessional care (e.g., medications like diuretics and beta blockers inheart failure patients) much sooner, thereby decreasing the likelihoodof the fluid accumulation developing into a more serious condition.

Determining the impedance values at which to notify a patient can provedifficult. Generally, patients should be notified every time they areapproaching a dangerously high fluid accumulation. However, notifyingpatients when they face less than dangerous fluid accumulation levelscan result in the unnecessary consumption of time and resources. Thiscan pose economic and cost challenges when the need to alert patients ismultiplied over a large patient population.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic diagram of an implantable medical device.

FIG. 2 is a schematic diagram of exemplary electrode configurations inan implantable medical device.

FIG. 3 is a schematic diagram of an implantable medical device in whichthe present invention may usefully be practiced.

FIG. 4 is a schematic diagram illustrating an exemplary method ofmeasuring impedance.

FIG. 5 is a flow chart illustrating an exemplary method by which asystem can monitor impedance data.

FIG. 6 is a plot of exemplary impedance measurements taken pursuant tothe method of FIG. 5.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The following detailed description of illustrative embodiments should beread with reference to the drawings, in which like elements in differentdrawings are numbered identically. The drawings depict illustrativeembodiments and are not intended to limit the scope of the invention.Rather, the present invention is defined solely by the claims andequivalents thereof.

FIG. 1 is a schematic diagram of an exemplary implantable medical device10 according to an embodiment of the present invention. A section of abody 11 is shown with a cut-away area 12 to allow for illustration of animplantable medical device 10. The implantable medical device 10includes two electrodes 15 a and 15 b on the surface of a shell 14 ofdevice 10. Power is provided to the circuitry internal to the shell 14by a power supply 18, which drives a stimulation circuit 16, sendingelectrons through various intra-thoracic pathways in the body betweenelectrodes 15 a and 15 b. The intra-thoracic pathways are illustrated asbeing primarily in the area surrounded by dotted line 13. An impedancemeasurement device 17 determines the impedance of the circuit pathway13.

FIG. 2 is a schematic diagram of exemplary electrode configurations inan implantable medical device. The different configurations can achievedifferent impedance measurement signal values. For example, theimplantable medical device has electrodes (e1), (e2), (eg), and (em).Electrode (e1) or electrode (e2) can be used for developing the testpulses. The value being measured (voltage or impedance of the tissuebetween these electrode pairs) is taken between one of three electrodepairs: (1) an electrically isolated measuring electrode (em) and theindifferent or ground electrode (eg), (2) electrode (em) and electrode(e1), or (3) electrode (em) and electrode (e2). Further, the measurementcould be taken between the two test pulse delivery electrodes (e1) and(eg), or between electrode (e2) and electrode (eg).

FIG. 3 is a schematic diagram of an exemplary implantable medical devicein which the present invention may usefully be practiced. Theimplantable medical device includes a hermetically sealed enclosure 111and three leads: a ventricular lead 105, an atrial/SVC lead 107, and acoronary sinus/coronary vein lead 109. The enclosure 111 contains theelectronic circuitry implemented for generating cardiac pacing pulsesfor delivering cardioversion and defibrillation shocks and formonitoring the patient's heart rhythm. Examples of such circuitry arewell known in the art. The ventricular lead 105 carries three electrodesadjacent its distal end: a ring electrode 124, an extendable helixelectrode 126 mounted retractably within an insulative electrode head128, and an elongated coil electrode 120. Similarly, the atrial/SVC lead107 carries three electrodes adjacent its distal end: a ring electrode121, an extendible helix electrode 117 mounted retractably within aninsulative electrode head 119, and an elongated coil electrode 123. Thecoronary sinus/coronary vein lead 109 carries an electrode 108(illustrated in broken outline) that is located within the coronarysinus and great vein of the heart. The coronary sinus/coronary vein lead109 also carries a ring electrode 125 and a tip electrode 127 adjacentits distal end.

FIG. 4 is a schematic diagram illustrating an exemplary method ofmeasuring impedance according to an embodiment of the present invention.To generate an intra-thoracic impedance Z_(m) measurement, a pacertiming and control circuit initiates, via control circuitry, delivery ofa predetermined voltage pulse V_(o) from an output circuit along anexcitation path 280 between electrodes 120 and 130. A resistor R_(o)having a known resistance is incorporated in the output circuit,positioned along the excitation path 280 so that the current I_(o)delivered along the excitation path 280 can be calculated, using Ohm'sLaw, as I_(o)=V_(o)/R_(o). The voltage V_(m) is measured across themeasurement path 282 between a point after resistor R_(o) and electrode130, and, knowing the current I_(o) delivered to the measurement path282, impedance Z_(m) is calculated asZ _(m) =V _(m)/(V _(o) /R _(o)).

According to certain embodiments of the present invention, raw impedancemeasurements are collected a predetermined number of times per day(e.g., one measurement every 20 minutes) during one or morepredetermined periods of the day (e.g., between noon and 5 μm). A dailymean impedance is determined by averaging the raw impedancemeasurements. An expected, or baseline (BL), impedance is computed bytaking a very low pass filtered version of the daily mean impedance. TheBL impedance is intended to represent the patient's “dry” impedance whenexcessive fluid is not present. The value of a BL impedance varies frompatient to patient and is generally between approximately 50 ohms and 90ohms. A short term average (STA) impedance is computed by taking aslightly filtered version of the daily mean impedance. The STA impedanceis intended to be a best estimate of the current impedance.

These measurements may, for example, be obtained from pre-programmedvectors chosen for the excitation path and the measurement path, such asthe ring (e3) to case (eg) and tip (e2) to case (eg) arrangement of FIG.2. Referring to FIG. 3, the RV coil electrode 120 and housing electrode130 may, for example, be utilized for both the excitation path and themeasurement path. However, it is understood that other arrangements canalso be utilized, such as an arrangement in which the excitation path isbetween electrode 123 and electrode 130 and the measurement path isbetween electrode 117 and electrode 130. Another operative vector couldbe an RV coil 120 to the enclosure 111 vector with a left pectoralimplant. Another could be a vector from an SVC coil 123 to an RV coil120. However, most any vector for impedance monitoring could be used. Itis further contemplated that the leads can be epicardial leads and/orsubcutaneous leads. Enclosure 111 can be implanted in a sub-muscular orsubcutaneous location anywhere about the chest. In some embodiments, theenclosure 111 is located in a region other than the pectoral region.

Once an initial stabilization time period has expired after implantation(e.g., 45 days), initial values of the BL impedance and the STAimpedance are established. Observing a stabilization period avoidsinaccurate (e.g., artificially low) impedance readings caused by fluidbuildup in the thoracic cavity stemming from the recovery fromimplantation of device. Once the BL impedance and the STA impedance areestablished, changes in the daily mean impedance values over time aremonitored for indications of fluid accumulation. Monitoring impedancedata is discussed in the following paragraphs and in U.S. PatentApplication Publication No. 2004/0172080 to Stadler et al., titled“Method and Apparatus for Detecting Change in Intrathoracic ElectricalImpedance,” which is incorporated by reference herein in relevant part.

FIG. 5 is a flow chart that shows an exemplary method by which a systemcan monitor impedance data according to the present invention. Thesystem first establishes the initial values of the BL impedance and theSTA impedance (505), as set forth above. Then the system receives adaily mean impedance (510) and updates the STA impedance and the BLimpedance (515), (520) based on that daily mean impedance. In someembodiments, the STA impedance is updated (515) by taking a weighted sumof (a) the STA impedance for the two previous days and (b) the dailymean impedance for the current day and the two previous days. In suchembodiments, the STA impedance can be relatively responsive to changesin the daily mean impedance. In many embodiments, the BL impedance isupdated (520) at a much slower rate than the STA impedance. The BLimpedance is updated (525) based on the STA impedance. That is, if thenewly-calculated STA impedance is less than the BL impedance, the BLimpedance is adjusted downward by a predetermined downdrift (e.g., 0.055ohms), and if the newly-calculated STA impedance is greater than the BLimpedance, the BL impedance is adjusted upward by a predeterminedupdrift (e.g., 0.18 ohms).

After updating the STA impedance and BL impedance (515), (520), thesystem can determine whether the impedance data indicates normal orabnormal fluid levels. This method is especially applicable when the STAimpedance measures consistently and significantly below the BLimpedance—a trend that could indicate abnormally high fluid levels.Accordingly, when a given STA impedance is either greater than thecorresponding BL impedance or within a predetermined hysteresis (X) ofthe corresponding BL impedance, it can be inferred that this trend isnot present and that fluid levels are normal.

With this in mind, after updating the STA impedance and the BL impedance(515), (520), the system can determine whether the newly-calculated STAimpedance is greater than the newly-calculated BL impedance less thepredetermined hysteresis value (X) (525). If it is, the system can reseta cumulative index of previous days' BL impedances minus correspondingSTA impedances (530). Resetting the cumulative index indicates that thetrend discussed above is not present. In some instances, a clinician caninitiate the reset (full or soft) manually. In such embodiments, themanual reset can be performed via telemetry, via a pushbutton on theenclosure, or via other suitable means. After resetting the cumulativeindex (530), the system can wait to receive the next daily meanimpedance (510), at which time the process can be repeated. If thenewly-calculated STA impedance is not greater than the newly-calculatedBL impedance less the predetermined hysteresis value (X), the systemupdates the cumulative index (535) by adding the difference between thenewly-calculated BL impedance and the newly-calculated STA impedance tothe cumulative index.

After updating the cumulative index (535), the system can determinewhether the updated cumulative index indicates abnormally high fluidlevels (540). In some embodiments, the system makes this determinationby comparing the cumulative index to a predetermined threshold, which isestablished by a clinician according to factors that are discussed inmore detail below. If the system determines that the cumulative indexdoes not indicate abnormally high fluid levels, the system can wait toreceive the next daily mean impedance (510), at which time the processcan be repeated. Alternatively, if the system determines that thecumulative index does indicate abnormally high fluid levels, the systemcan notify the patient (545) (e.g., by an audible alarm, by vibration,by stimulation, by communication to an external device, etc.).

In addition, in some embodiments, the system can modify the algorithmfor detecting changes in impedance in response to the detection ofabnormally high fluid levels. For example, the interval at which thedaily mean impedance is calculated could be increased (e.g., from onceper day to once per hour). In such embodiments, the system firstdetermines whether to modify the algorithm (550). If the systemdetermines that it should not modify the algorithm, the system can moveon to the next step. If the system determines that it should modify thealgorithm, the system does so (555) and then moves on to the next step.In some embodiments, the system can initiate or modify therapy when anabnormally high fluid level is detected. In such embodiments, the systemfirst determines whether to initiate or modify therapy (560). If thesystem determines that it should not initiate or modify therapy, thesystem can wait to receive the next daily mean impedance (510) (whilethe patient hopefully seeks professional care), at which time theprocess can be repeated. If, on the other hand, the system determinesthat it should initiate or modify therapy, the system does so (565).Examples of such therapy include activating a drug pump, a pacing mode,or a pacing rate, or performing cardiac resynchronization therapy (CRT)or cardiac potentiation therapy (CPT). After initiating or modifyingtherapy, the system can wait to receive the next daily mean impedance(510) (while the patient hopefully seeks professional care), at whichtime the process can be repeated.

The order of steps provided in the methods shown in FIG. 5 is providedfor purposes of illustration only, and other orders that achieve thefunctionality recited are within the scope of the present invention. Anyof the functionality discussed anywhere in this disclosure may beimplemented in the method shown in FIG. 5.

FIG. 6 shows a plot 600 of exemplary impedance measurements takenpursuant to the method of FIG. 5. Referring to FIG. 6, the plot 600 hasimpedance (measured in ohms) as its Y-axis and time (measured in days)as its X-axis. Values represented on the plot 600 include daily meanimpedance values 605, STA impedance values 610, BL impedance values 615,the cumulative index 620, and the predetermined threshold 625. Asdiscussed above, each daily mean impedance value 605 impacts that day'sSTA impedance value 610 and BL impedance value 615, with the STAimpedance values 610 being more responsive to changing daily meanimpedance values 605. As also discussed above, the cumulative index 620is impacted by the difference between the BL impedance values 615 andthe STA impedance values 610. Specifically, that difference for a givenday is added to that difference from previous days, unless that day'sSTA impedance value 610 is greater than that day's BL impedance value615 less a predetermined hysteresis value, in which case the cumulativeindex 620 is reset. Once the cumulative index 620 reaches thepredetermined threshold 625, the patient is notified, therapy isinitiated or modified, and/or the algorithm is modified, as discussedabove. As can be seen from the plot 600, the patient is notified on Day630, Day 632, and Day 634.

In the system of plot 600, the predetermined hysteresis is set at zeroohms. As a result, a day's STA impedance value 610 must exceed thecorresponding BL impedance value 615 to reset the cumulative index 620.This occurs on Day 636, Day 638, and Day 640, among others.

While systems that reset the cumulative index when a day's STA impedancevalue 610 exceeds the day's BL impedance value 615 are remarkablysuccessful in detecting abnormal fluid accumulation levels, they cansometime result in an inordinately high number of false positives. Whena patient is notified of a possible fluid build-up, he or she typicallyseeks professional care relatively quickly. A clinician then determineswhether the patient does, in fact, have abnormal fluid accumulation. Ifthe patient has abnormal fluid accumulation, he or she receivestreatment to restore proper fluid levels (e.g., intravenous diuretics).If the patient does not have abnormal fluid accumulation (i.e., thefluid build-up notification was a false positive), he or she may leavethe professional care facility without receiving any treatment. Suchfalse positives consume valuable time and resources, both of theclinician and of the patient.

One approach to reduce the number of false positives is to increase thepredetermined threshold 625. If the cumulative index 620 must reach ahigher value before notifying the patient, there will likely be fewer ofsuch notifications. For example, if the predetermined threshold 625 wereset to 60 ohm-days rather than 55 ohm-days, neither Day 632 nor Day 634would result in patient notifications. The downside of increasing thepredetermined threshold 625 is decreased sensitivity. In other words,the system may fail to notify the patient when the patient is actuallyexperiencing abnormally high fluid accumulation levels.

Yet another approach to reduce the number of false positives whileretaining the desired sensitivity is to increase the predeterminedhysteresis value to a value greater than zero ohms. In other words, insuch systems, the cumulative index 620 is reset, not when the STAimpedance value 610 exceeds the BL impedance value 615, but when the STAimpedance value 610 comes within the hysteresis value of the BLimpedance value 615. For example, the patient represented in plot 600was notified falsely of abnormally high fluid levels three times (on Day630, Day 632, and Day 634); he or she never had abnormally high fluidlevels. Increasing the hysteresis value would have resulted in thecumulative index 620 being reset on days in which the STA impedancevalue 610 was close to as high as the BL impedance value 615 (e.g., onDay 642 or Day 644). In many instances, resetting the cumulative index620 on such days would prevent the patient from unnecessarily seekingprofessional care, thereby saving time and resources. In plot 600, ifthe cumulative index 620 were reset on Day 642 and Day 644, the patientwould not likely have been falsely notified on Day 630 or Day 632.

A clinician can determine the appropriate hysteresis value based on avariety of factors. For example, in some instances, the size of theimplantable medical device that houses the system can impact thehysteresis value. This is because the implantable medical device acts asone of the poles of the impedance measurement (see FIG. 4). A largerimplantable medical device often results in larger initial impedancevalues, and a smaller implantable medical device often results insmaller initial impedance values. Accordingly, a smaller hysteresisvalue should be used with a larger implantable medical device, and alarger hysteresis value should be used with a smaller implantablemedical device. In other words, the hysteresis value can be a percentageof the initial impedance values. Likewise, in some instances, the natureof the patient can impact the hysteresis value. For some patients, thedaily mean impedance values 605 vary widely from one day to the next,whereas for others, the daily mean impedance values 605 vary onlyminimally. A clinician can determine the patient's variability level byreviewing the patient's impedance values taken during the initializationphase. A larger hysteresis value should be used for patients whose dailymean impedance values 605 vary widely, and a smaller hysteresis valueshould be used for patients whose daily mean impedance values 605 varyonly minimally.

The technique of adding a hysteresis value to an intra-thoracic fluidmonitoring algorithm has been described and depicted in the context ofintra-thoracic impedance measurement. This technique, however, could beapplied to systems measuring many types of physiological variables(e.g., pressure).

Some of the techniques described herein may be embodied as acomputer-readable medium comprising instructions for a programmableprocessor. The programmable processor may include one or more individualprocessors, which may act independently or in concert. A“computer-readable medium” includes but is not limited to any type ofcomputer memory such as floppy disks, conventional hard disks, CR-ROMS,Flash ROMS, nonvolatile ROMS, RAM and a magnetic or optical storagemedium. The medium may include instructions for causing a processor toperform any of the features described above.

Certain embodiments may have one or more of the following advantages. Insome embodiments, the number of so-called “false positive” detection ofpulmonary edema is decreased. In some embodiments, the sensitivity fornotifying patients in “true positive” situations is retained. In someembodiments, the number of so called “false positives” can be decreasedwithout adjusting the predetermined threshold. Some embodiments areadjustable for different kinds of implantable medical devices. Someembodiments are adjustable for different kinds of patients. Someembodiments are able to make use of intra-thoracic impedance datagathered during the system's initialization period.

Thus, embodiments of the present invention are disclosed. One skilled inthe art will appreciate that the present invention can be practiced withembodiments other than those disclosed. The disclosed embodiments arepresented for purposes of illustration and not limitation, and thepresent invention is limited only by the claims that follow.

1. A method of monitoring fluid levels by an implantable device, comprising: the device taking a series of intra-thoracic impedance measurements from a patient; the device modifying a short-term impedance value based on the series of intra-thoracic impedance measurements; the device modifying a baseline impedance value based on the series of intra-thoracic impedance; the device adding a difference of the baseline impedance value minus the short-term impedance value to a cumulative index in response to the short-term impedance value being less than the baseline impedance value minus a predetermined positive hysteresis value; the device resetting the cumulative index in response to the short-term impedance value being greater than the baseline impedance value minus the hysteresis value; and the device notifying the patient of possible fluid accumulation in response to the cumulative index exceeding a predetermined threshold value.
 2. A method according to claim 1, further comprising calculating an average value of the series of intra-thoracic impedance measurements, wherein modifying the short-term impedance value and the baseline impedance value is based on the average value.
 3. A method according to claim 1, wherein the hysteresis value is based on a physical characteristic of the implantable medical device.
 4. The method of claim 3, wherein the physical characteristic includes the size of the implantable medical device.
 5. A method according to claim 1, wherein the series of intra-thoracic impedance measurements from the patient include a degree of variation from day to day, and wherein the hysteresis value is based on the degree of variation.
 6. A method according to claim 1, further comprising calculating an initial baseline impedance value.
 7. A method according to claim 6, wherein the predetermined hysteresis value comprises a percentage of the initial baseline impedance value.
 8. A method according to claim 1, further comprising initiating therapy to the patient or modifying therapy being provided to the patient in response to the cumulative index exceeding the predetermined threshold value.
 9. A method according to claim 1, wherein the step of the device notifying the patient of possible fluid accumulation in response to the cumulative index exceeding a predetermined threshold value is selected from the group consisting of (a) sounding an audible alarm, (b) vibrating, (c) causing stimulation, (d) communicating to an external medical device, and (e) combinations of two or more of (a)-(d).
 10. An implantable medical device, comprising: a hermetically-sealed enclosure carrying an enclosure electrode; a lead functionally coupled to the enclosure and carrying a lead electrode; and circuitry housed within the enclosure, the circuitry being configured to: take a series of intra-thoracic impedance measurements from a patient via the enclosure electrode and the lead electrode, modify a short-term impedance value and a baseline impedance value based on the series of intra-thoracic impedance measurements, add a difference of the baseline impedance value minus the short-term impedance value to a cumulative index in response to the short-term impedance value being less than the baseline impedance value minus a predetermined positive hysteresis value, reset the cumulative index in response to the short-term impedance value being greater than the baseline impedance value minus the hysteresis value, and trigger a notification relating to possible fluid accumulation in response to the cumulative index exceeding a predetermined threshold value.
 11. An implantable medical device according to claim 10, wherein the enclosure has a characteristic size, and the predetermined positive hysteresis value is based on the characteristic size.
 12. An implantable medical device according to claim 10, wherein the series of intra-thoracic impedance measurements from the patient have a degree of variation from day to day, and wherein the hysteresis value is based on the degree of variation.
 13. An implantable medical device according to claim 10, wherein the circuitry calculates an initial baseline impedance value.
 14. An implantable medical device according to claim 13, wherein the hysteresis value comprises a percentage of the initial baseline impedance value.
 15. A method of monitoring fluid levels by an implantable device, comprising: the device calculating an initial baseline impedance value; the device taking a series of intra-thoracic impedance measurements from a patient; the device calculating an average value of the series of intra-thoracic impedance measurements; the device modifying a short-term impedance value based on the average value; the device modifying a baseline impedance value based on the average value; adding a difference of the baseline impedance value minus the short-term impedance value to a cumulative index in response to the short-term impedance value being less than the baseline impedance value minus a predetermined positive hysteresis value, wherein the hysteresis value is a percentage of the initial baseline impedance value; the device resetting the cumulative index in response to the short-term impedance value being greater than the baseline impedance value minus the hysteresis value; and the device generating a notification signal in the event that the cumulative index exceeds a predetermined threshold value.
 16. A method according to claim 15, wherein the series of intra-thoracic impedance measurements from the patient have a degree of variation from day to day, and wherein the hysteresis value is based on the degree of variation.
 17. A method according to claim 15, further comprising initiating therapy to the patient or to modify therapy being provided to the patient in response to the cumulative index exceeding the predetermined threshold value. 